Hypothesis: Therapies aimed at negatively modulating specific targets upstream of, within or downstream of the TGF13 signaling pathway may prevent neonatal lung injury, augment neonatal lung repair and hence optimize alveolar formation. Aim 1. Candidate gene induction in the upstream cascade: to determine the impact of neonatal hyperoxia and/or LPS endotoxin on time and space-specific expression and activity of ILll3 and TNFo_, their cognate receptors, Toll family LPS endotoxin receptors and TGF13 expression and signaling in neonatal lung. Aim 2. Candidate upstream target gene function: to compare the impact of neonatal hyperoxi_ and/or LPS endotoxin, versus local overexpression of IL1-13, or TNF-_, or TGF-(_ using recombinanl viral vectors to determine which of them most closely phenocopies BPD by abrogation ol alveolarization. Aim 3. Synergy between candidate upstream target genes: to determine whether synergy tc abrogate formation of alveoli exists between neonatal hyperoxia, LPS endotoxin, ILl13, TNFo_, and/or TGF-13 in our neonatal rat model. Aim 4. Smad3 as a common downstream target mechanism: to discover whether the effects ol neonatal hyperoxia, and/or LPS endotoxin injury as well as of ILll3, TNF(_, and/or TGF13 signaling ir neonatal lung are transduced through a common TGF-odSmad3 signaling pathway, using the Smad,_ null mouse as a test model. Aim 5. Protection: to determine whether the negative sequelae of neonatal hyperoxia and/or LP5 endotoxin injury on alveolar formation can be blocked or ameliorated, either upstream or downstrearr within the TGF-13 pathway using recombinant viruses expressing Decorin or Smad7.